InterSV

  Interpret Structure Variant

 InterSV - Structure Variant Interpretation

Evidence system

ACMG introduces a quantitative, evidence-based scoring framework; encourages the implementation of the five-tier classification system widely used in sequence variant classification; and recommends "uncoupling" the evidence based classification of a variant from its potential implications for a particular individual.The ACMG professional standards will guide the evaluation of constitutional CNVs and encourage consistency and transparency across clinical laboratories. We aligned and extended these ACMG/AMP/ClinGen guidelines for structure variants(SVs). The evidence category include: 1.Initial assessment of genomic content;2.Established (or Predicted) Pathogenic or Benign Dosage Sensitive Genes/Genomic Regions;3.Evaluation of Gene Number;4.Detailed Evaluation of Genomic Content Using Cases from Published Literature, Public Databases;5.Evaluation of Inheritance Pattern/Family History.

Score system

The standards build by introducing a semiquantitative point-based scoring metric for classification. In general,scores for each observed piece of evidence, both in support of (positive values) and refuting (negative values) pathogenicity, are summed to arrive at a final classification. SVs with a final point value >=0.99 are considered pathogenic, while point values between 0.90 and 0.98 are consided likely pathogenic; The variant of uncertain significance (VUS) category is the broadest, corresponding to points between −0.89 a 0.89 ,while refutinnng evidence arriving at scores between −0.9 and 0, <=-0.90 are considered likely benign and benign, respectively.

Help/Tutorial

1.Choose the genomic version and proper variant information.

Before the variant searching, the user need to select the genomic version(currently, support hg19 and hg38) and variant type.
InterSV support 3 types of structure variants: deletion, duplication and translocation.

2.Choose the searching method

When searching one variant user need check :
Single:
Use need to input the variant location such as chromosome, start and end.

When searching multiple variants, user need check :
Batch:
Use need to input the variants location such as chromosome, start ,end and type in the textarea


3.Click submit to go to pre-result page.

Submit the query.

4.Manually input the variant information based on user's experience and submit.

4.1 Variant information.
In this page , followed by two tables, InterSV will give the options for the variant:
In Section-4 and Section-5, user can click or change the values for the variant based on knowledge

4.2 Submit.
Submit the query will bring to the results.

5.Review the interpretation result.

5.1 Interpretation evidence.
In these cards, InterSV will give the evidence detail.
Followed by five cards: Section-1 to Section-5.

5.2 Interpretation Overview.
This card provide interpretation result as Pathogenic,Likely Pathogenic, Unknown significance or Benign/Likely Benign.


Reference

1.Erin Rooney Riggs et al. Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8
2.Sue Richards et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30.
3.Quan Li and Kai Wang. InterVar: Clinical interpretation of genetic variants by ACMG-AMP 2015 guideline(The American Journal of Human Genetics 100, 1-14, February 2, 2017,http://dx.doi.org/10.1016/j.ajhg.2017.01.004)

Please cite:

Quan Li, YunYun Zhou and Kai Wang. InterSV: a web server for evidence-based clinical interpretation of structure variants. (In Preparation,2021)
Copyright © InterSV